The goals of the proposed research are first, to examine the influences of hypoxia, acidosis, and the level of diaphragmatic energy expenditure on diaphragmatic energy metabolism, and second to assess the impact of emphysema on diaphragm muscle mass and fiber length. The first set of experiments will be conducted using an animal model of acute respiratory failure in which diaphragmatic energy expenditure is increased 10-15 fold. We have shown that hypoxia, acidosis and increased energy expenditure severely deplete diaphragm muscle tissue, phosphocreatine (PC) and ATP levels without increasing diaphragm muscle lactate. It remains to establish the separate effects of these factors using a level of inspiratory flow resistance which does not induce hypoxemia or hypercapnia, and administering either a hypoxic or hypercapnic gas mixture to breathe. To assess the effect of chronic alterations in the resting position of the diaphragm on the dimensions and structure of diaphragm muscle, the mass, area, and thickness of the muscular part of the diaphragm will be measured in the hamster model of elastase-induced emphysema. The purpose of both groups of studies is to evaluate the ability of the diaphragm to maintain ventilation under conditions which approximate those encountered in human obstructive lung disease and acute respiratory failure.